Delayed Onset of Chronic GVHD in Patients Receiving RGI-2001 Prophylaxis: A Multicenter Phase 2b Study with Comparison to CIBMTR Matched Cohort Data

Document Type

Conference Proceeding

Publication Date

2-1-2026

Publication Title

Transplant Cell Ther

Keywords

methotrexate, tacrolimus, acute graft versus host disease, adult, chronic graft versus host disease, cohort analysis, conference abstract, controlled study, drug therapy, female, graft versus leukemia effect, human, immunocompetent cell, immunological tolerance, immunomodulation, incidence, major clinical study, male, multicenter study, prevention, prophylaxis, regulatory T lymphocyte, risk factor, risk model, therapy

Abstract

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity following allogeneic hematopoietic cell transplantation (allo-HCT). The timing of cGVHD onset may impact outcomes and guide prevention strategies. RGI-2001, expands regulatory T-cells (Tregs), and demonstrated efficacy in preventing acute GVHD when combined with tacrolimus/methotrexate (TAC/MTX) (Blood, July 2025). However, its impact on cGVHD has not been characterized. We analyzed 48 patients receiving myeloablative allo-HCT and prophylaxis with RGI-2001 (weekly through day +35). cGVHD was assessed per NIH criteria, and cumulative incidence (CI) was estimated using competing risk models. cGVHD cases were stratified using day ≤120 as early onset and day >120 as later-onset. Earlier onset may indicate alloimmune activation, while later onset may reflect delayed immune cell reconstitution dysfunction. The 1-year CI of moderate-to-severe cGVHD for RGI-2001 and CIBMTR was 33.3% and 33.2% respectively. The median time to cGVHD onset was 211 days (range: 84–275); one patient (2.1%) experienced early-onset cGVHD (≤ day +120) and 31.2% of patients later-onset cGVHD (> day +120) in RGI-2001 cohort. In comparison, the median cGVHD onset was 119 days with 9.1% early-onset and 24.1% later-onset in CIBMTR cohort. RGI-2001 group showed a significantly lower rate of early-onset cGVHD (p = 0.044, Fisher's exact test, Figure 1). Demographics and cGVHD risk factors were comparable between groups (Table 1). Authors acknowledge the limitation of registry data comparison. RGI-2001 appears to shift the temporal onset of cGVHD, significantly reducing early cases and delaying onset beyond day +120. This effect may be driven by Treg-mediated immunomodulation beyond the dosing window; potentially benefiting graft versus leukemia response and altering the pathogenesis of cGVHD. RGI-2001 induces Tregs which engages CD1d high B cell uptake and promote immunoregulation through NKT-Treg interactions (Ishii 2008). These findings support investigation in extending RGI-2001 administration to enhance long-term immune tolerance and reduce cGVHD incidence.

Volume

32

Issue

2

First Page

S277

Last Page

S278

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